Exhibit 4.33


 


Date:  4th
August 2003


 


 


AMARIN CORPORATION PLC.


 


AND


 


ELAN PHARMA INTERNATIONAL LIMITED


 


 


AMENDED AND RESTATED OPTION AGREEMENT


(ZELAPARTM)


 

















 


INDEX


 


	
  1.

  	
  Rights
  Subject to Option; Information Provided to Amarin

  	
   

  
	
   

  	
   

  	
   

  
	
  2.

  	
  Evaluation by Amarin

  	
   

  
	
   

  	
   

  	
   

  
	
  3.

  	
  Option to License

  	
   

  
	
   

  	
   

  	
   

  
	
  4.

  	
  Steering Committee

  	
   

  
	
   

  	
   

  	
   

  
	
  5.

  	
  Confidentiality

  	
   

  
	
   

  	
   

  	
   

  
	
  6.

  	
  Representations,
  Warranties and Covenants

  	
   

  
	
   

  	
   

  	
   

  
	
  7.

  	
  Financial
  Terms; Milestone Payments, Royalty

  	
   

  
	
   

  	
   

  	
   

  
	
  8.

  	
  Termination

  	
   

  
	
   

  	
   

  	
   

  
	
  9.

  	
  Default

  	
   

  
	
   

  	
   

  	
   

  
	
  10.

  	
  Miscellaneous.

  	
   

  
	
   

  	
   

  	
   

  
	
  EXHIBIT
  A

  	
  PATENT
  RIGHTS

  	
   

  



 

















 


CONFIDENTIAL


 


THIS AMENDED AND RESTATED
AGREEMENT
is made the 4th August 2003


 


BETWEEN:


 


(1)                                 AMARIN CORPORATION PLC, a company incorporated in
England and Wales (registered no. 002353920), whose registered office is 7
Curzon Street, London, W1J 5HG England (“Amarin”); and


 


(2)                                 ELAN PHARMA INTERNATIONAL LIMITED,  a company incorporated in  the
Republic of Ireland, whose registered office is at WIL House, Shannon Business
Park, Shannon, Co Clare, Ireland (“Elan”),


 


each
for themselves and their respective affiliates


 


RECITALS:


 


(A)                              Elan is the owner or exclusive
licensee of certain Rights (as defined below) relating to a Zydis® formulation
of selegeline hydrochloride (the “Product”) presently known as ZelaparTM,
which may have utility in the treatment of Parkinson’s disease and other
diseases or conditions.


 


(B)                                By an Option Agreement dated
18 June 2001, as amended by Deed of Variation dated 27 January 2003,
Amarin acquired an exclusive option for a transfer and assignment of such
Rights in the Territory in the Field, each as defined below.


 


(C)                                Elan and Amarin wish to vary
the terms of the said option, on the terms and conditions set out in this
Agreement.  On the date of entering into
this Agreement, the parties and certain affiliates of Elan have entered into an
Amended and Restated Master Agreement (the “Master Agreement”).


 


(D)                               Elan and Amarin, should Amarin
exercise its Option (as defined below), wish to enter into an Assignment Agreement
for the Rights in the Territory in the Field; and in the meantime, have
established a steering committee for the management of the completion of
development of Zelapar in the Territory.


 


AGREEMENT:


 


NOW,
THEREFORE, in consideration of the foregoing and the mutual covenants set forth
below, the parties hereby agree as follows:


 


1.                                           Rights Subject to Option; Information Provided to Amarin


 


1.1.                                   Definitions and Interpretation.  In this Agreement:


 


1.1.1                             “this Agreement” shall mean
this Amended and Restated Option Agreement, including its recitals, schedules
and exhibits.


 


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1.1.2                             “Original Agreement” shall
mean the Option Agreement dated 18 June 2001 between Amarin and Elan, as
amended by Deed of Variation dated 27 January 2003.


 


1.1.3                             “Demandable Date” has the same
meaning as in the Master Agreement.


 


1.1.4                             “Elan Agreement(s)” has the
same meaning as in the Master Agreement.


 


1.1.5                             the singular includes the
plural and vice versa; references to words in one gender include references to
the other genders; and references to natural persons includes corporate bodies,
partnerships and vice versa;


 


1.1.6                             any reference to a Clause,
Section or Schedule, unless otherwise specifically provided, is to a
Clause, Section or Schedule of or to this Agreement;


 


1.1.7                             the headings in this Agreement
are inserted for convenience only and do not affect its construction or
interpretation;


 


1.1.8                             the expressions “include”,
“includes”, “including”, “in particular” and similar expressions shall be
construed without limitation.


 


1.2.                                   Rights Defined.  For the purposes of this Agreement, “Rights” shall mean all of
Elan’s right, title and interest in any data, information, or know-how
pertaining to, and any license or other rights in, the Product in the
Territory, now owned or controlled or hereafter acquired by Elan.  By way of illustration, the foregoing Rights
shall include but not be limited to (i) all of Elan’s rights under the License and
Supply Agreement between Elan or its affiliates and RP Scherer and Company, as
amended (the “Scherer Agreement”), as it pertains to the Territory, and (ii)
all clinical, preclinical and other data, protocols, inventory, work in
progress, regulatory rights or applications of any kind (such as a New Drug
Application (“NDA”) for the Product), contract rights, market research,
patent rights, patent applications, trademark rights, trademark applications,
and any know-how associated with the Product for use in the Territory.


 


1.3.                                   Information.  Elan shall continue to provide Amarin with continuing access to
and, as appropriate, copies or samples of materials it has within its
possession or control which are the subject of the Rights, together with all
additional information, data, patent or trademark disclosures and know-how
relating thereto now known to or hereafter developed or obtained by Elan during
the Option Period (as defined below) (the “Information”), all on the terms and subject
to the conditions of this Agreement.


 


2.                                           Evaluation by Amarin


 


2.1.                                   Right to Evaluate.  During the Option Period, Amarin shall have the continuing right
to review the Information as Amarin determines is necessary to evaluate its
interest in exercising the Option. 
During the Option Period, Amarin shall use the Information


 


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solely for
that purpose.  Elan shall make the
Information available at its expense at 800 Gateway Blvd, South San Francisco,
California 94080.


 


2.2.                                   Return of Information if
Option not Exercised.  If this
Option is terminated or expires unexercised, Amarin shall return to Elan,
within thirty (30) days following the termination of the Option Period, all
Information of Elan and all copies thereof (or Amarin’s written confirmation
that it has destroyed all such copies), except for one complete set of
Information which Amarin may retain and use solely for compliance purposes
under the confidentiality requirements of this Agreement.


 


3.                                           Option to License


 


3.1.                                   Grant of Option.


 


(a)                             Elan hereby grants to Amarin
the following exclusive option (the “Option”), during the Option Period, to
obtain an exclusive transfer and assignment of the Rights, on the terms stated
below, to use, promote, distribute and sell the Product in the Territory, for
use in the field of human therapeutic treatment of any disease, condition or
disorder (the “Field”).  It is
understood and agreed that Elan retains all rights in the Product outside the
Territory which it now or hereafter may own or control.  For the purposes of this Agreement, the
Territory shall mean the United States.


 


(b)                            This Option is exercisable by
written notice to Elan received at any time during the Option Period.  If Amarin timely and properly exercises the
Option, the parties promptly shall negotiate in good faith and execute a
mutually acceptable definitive assignment agreement (the “Assignment Agreement”) which
shall incorporate the terms and conditions set forth in this Agreement and
shall include other terms and conditions which are reasonable and customary in
transactions of this nature.


 


(c)                             If the parties are unable to
agree upon the form of the Assignment Agreement within thirty days of the date
of the exercise of the Option, the parties shall submit any outstanding issues
to senior management of each party, who shall negotiate in good faith a
resolution.  If thirty days after such
submission to senior management issues remain unresolved, either party may
submit its proposed Assignment Agreement to an arbitrator in the San Francisco,
California area, selected under the then-current Commercial Rules of the
American Arbitration Association, who will select one of the two proposed
agreements, in its entirety.  The
arbitrator’s decision will be final, binding and enforceable in a court of
competent jurisdiction in San Francisco, California, which shall have exclusive
jurisdiction over the matter.


 


(d)                            Among other things, the
Assignment Agreement shall provide that Amarin shall assume and perform Elan’s
obligations under the Scherer Agreement as of the


 


4

















 


date of the transfer and assignment of the Rights; that in the event of
a conflict between the Scherer Agreement and the Assignment Agreement, the
Scherer Agreement shall control; and that the parties shall cooperate
reasonably to enable the other to fulfill their respective remaining
obligations under the Scherer Agreement in and outside the Territory.


 


3.2.                                   Option Period.  The “Option Period” shall mean the period
commencing on the date of this Agreement and ending on the sooner of (a) the
date on which Elan or any of its Affiliates which are a party to the Master
Agreement have received a total between them of US$30,000,000 (thirty million
dollars) pursuant to Clauses [7 and 8] of the Master Agreement or otherwise expressed
to be in discharge of the Outstanding Amounts (as defined in the Master
Agreement) and (b) 31 December 2003.


 


3.3.                                   Option Fees.  In consideration for the Option granted to Amarin, Amarin has
paid to Elan a non-refundable, non-creditable option fee of One Hundred
Thousand Dollars ($100,000).  The option
fee, together with the payments to Elan under the Master Agreement, shall be
full consideration for the grant of the Option.


 


3.4.                                   Conditions for, and Deemed
Exercise of, the Option.  Amarin shall
be deemed to have exercised the Option (if available at the time in question)
upon providing the certification referred to in Clause [8.6] of the Master
Agreement; and no other exercise of the Option shall be permitted unless such
certification is made within the Option Period.  Amarin shall provide to Elan like certification upon execution of
the Assignment Agreement.


 


3.5.                                   Pursuit of New Drug
Application.  During the Option Period,
Elan shall subject to Section 4.4 be responsible for and shall use Commercially
Reasonable Efforts to diligently pursue the preparation, submission, acceptance
for filing and substantive review, and approval of an NDA for the Product with
the FDA; shall continue the prosecution and maintenance of all its patents,
patent applications, trademarks and trademark applications included in the
Rights; and shall consult with and consider the reasonable requests of Amarin
in connection with the above.  “Commercially
Reasonable Efforts” of a Party shall mean efforts consistent with
the exercise of its prudent business judgment as applied to other clinical,
regulatory and commercialization efforts for products of similar performance
and potential as would be undertaken in the pharmaceutical industry, but not
less than those efforts applied by that Party to other similar products of its
own product line.


 


4.                                           Steering Committee


 


4.1.                                   Formation of Steering
Committee.  The parties have formed a Zelapar Steering
Committee consisting of an equal number of Elan and Amarin members.  The chair of the Steering Committee shall
rotate between Elan and Amarin at least annually.  Elan and Amarin may each designate a proxy or substitute for its
members, and may substitute its members.


 


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4.2.                                   Steering Committee Meetings;
Project Plan.  The Steering Committee will
meet no less than quarterly at a site to be mutually agreed, with minutes and
next quarter objectives to be distributed by the chair and approved; each party
will pay its own expenses in attendance and related activities.  A draft of the plan for completion of
development and approval of an NDA for the Product (the “Plan”) has been drafted by
Elan for review and approval, not to be unreasonably withheld, by Amarin.  The Plan contains milestone events and
timelines for review and approval by the Steering Committee.  Thereafter, the Plan may be amended only by
majority vote of the Steering Committee. 
Material deviations in executing the Plan must be approved in advance by
the Steering Committee.  It is understood
and agreed that Elan will perform and manage the day-to-day execution and
operations of the Plan.  Disputes not
resolved by the Steering Committee within fourteen (14) days shall be referred
to respective company senior management for good faith discussion and
resolution.


 


4.3.                                   Project Team.  In addition to the Steering Committee, Amarin shall be entitled
to attend and participate in and receive all materials provided to Elan’s
Project Team for Zelapar.


 


4.4.                                   Expenses.  The costs and expenses associated with the parties’ respective
performance of their obligations under this Agreement shall be borne as
follows:


 


(a)                             Elan will bear all costs and
expenses (internal and external) incurred prior to 31 December 2002 (the “Amendment
Date”) and associated with performing its obligations under this
Agreement, including without limitation Section 3.4 above, and the
implementation of the Plan prior to the Amendment Date.


 


(b)                            Subject to Section 4.5,
Amarin shall be responsible for all reasonable and verifiable Out Of Pocket
Costs after the Amendment Date, whether incurred by Elan, Amarin or a third
party where such Out Of Pocket Costs have been approved by the Steering
Committee and such Out Of Pocket Costs are not attributable to a negligent act
or omission or breach of the terms of this Agreement or the Assignment
Agreement by, or on behalf of, Elan.


 


(c)                             Each party shall be
responsible for its costs and expenses which are not Out Of Pocket Costs in
connection with (i) Elan’s activities pursuant to Section 3.4 and/or (ii)
the implementation of the Plan, incurred on or after the Amendment Date.


 


For the purposes of this Section 4.4,
“Out Of
Pocket Costs” shall mean all amounts payable to third parties,
including without limitation contractors, incurred on or after the Amendment
Date in connection with (i) Elan’s activities pursuant to Section 3.4
and/or (ii) the implementation of the Plan.


 


4.5.                                   Process and Audit.


 


(a)                                  Within 15 days of the end of
each calendar month following the Amendment Date, Elan and Amarin shall provide
to each other a statement


 


6

















 


of their Out
Of Pocket Costs incurred in the previous calendar month.  Within 15 days thereafter, Amarin shall pay
to Elan an amount equivalent to such Out Of Pocket Expenses of Elan.


 


(b)                                 For the 90 day period
following the close of each calendar year, Amarin and Elan will, in the event
that the other party reasonably requests such access, provide each other’s
independent certified accountants (reasonably acceptable to the other party)
with access, during regular business hours and subject to the confidentiality
provisions as contained in this Agreement, to such party’s books and records
relating to Out Of Pocket Costs, solely for the purpose of verifying the accuracy
and reasonable composition of the calculations hereunder for the calendar year
then ended.


 


(c)                                  In the event of a discovery of
a discrepancy which exceeds five per cent (5%) of the amount due or charged by
a party for any period, the cost of such audit shall be borne by the audited
party; otherwise, such cost shall be borne by the auditing party.


 


5.                                           Confidentiality


 


5.1.                                   Confidential Information.  Except as otherwise provided in this Section 5, during the
Option Period, each party shall maintain in confidence all information of the
other party (including any Product samples) disclosed by the other party under
the Agreement (the “Confidential Information”), and shall not
use, disclose or grant the use of the Confidential Information of the other
party, except to its and its affiliates’ directors, officers, employees,
permitted assignees, agents, consultants, clinical investigators and
contractors, to the extent such disclosure is reasonably necessary in
connection with such party’s activities as expressly authorized by the
Agreement.  To the extent that
disclosure is authorized by the Agreement, prior to disclosure, each party
hereto shall obtain agreement of any such person or entity to hold in
confidence and not make use of the Confidential Information for any purpose
other than those permitted by the Agreement. 
Each party shall notify the other promptly of any unauthorized use or
disclosure of the other party’s Confidential Information.


 


5.2.                                   Permitted Disclosures.  The confidentiality obligations contained in Section 5.1
above shall not apply to the extent that (a) the receiving party (the “Recipient”)
is required to disclose Confidential Information by law, order or regulation of
a governmental agency or a court of competent jurisdiction, provided that the
Recipient shall provide to the disclosing party written notice and sufficient
opportunity to object to such disclosure or to request confidential treatment
thereof; or (b) the Recipient can demonstrate that (i) the Confidential
Information was public knowledge at the time of such disclosure by the
Recipient, or thereafter became public knowledge, other than as a result of
actions of the Recipient, its affiliates and licensees in violation hereof;
(ii) the Confidential Information was rightfully known to or independently
developed by the Recipient, its affiliates or licensees (as shown by its
written records) prior to the date of disclosure to the Recipient


 


7

















 


by the other
party hereunder; or (iii) the Confidential Information was received by the
Recipient, its affiliates or licensees on an unrestricted basis from a source
unrelated to any party to the Agreement and not under a duty of confidentiality
to the other party.


 


5.3.                                   Terms of the Agreement and Use
of Name.  Except as otherwise provided in Sections 2.2
and 5.2 above, Elan and Amarin shall not disclose any terms or conditions of
the Agreement to any third party without the prior consent of the other party,
not to be unreasonably withheld.


 


6.                                           Representations, Warranties and Covenants


 


6.1.                                   Elan.  Elan represents and warrants that it has the full right and
authority, and has taken all necessary corporate action, to provide access to
the Information, grant Amarin the exclusive Option and, if exercised, enter
into the Assignment Agreement as set forth in this Agreement.  Elan warrants that Elan’s entering into and
performing this Agreement will not conflict with or create a default under any
agreement or obligation binding on Elan or any of the assets or property which
are the subject of this Agreement.  Elan
further warrants that:


 


(a)                             it is the sole owner or
exclusive licensee of the Rights (with full right to grant the option and
transfer and assign under any license agreement), without the necessity of
obtaining any consents of third parties other than Scherer, and that such
right, title and interest is unencumbered by any lien, charge, claim or
encumbrance of any kind; and


 


(b)                            it is the sole owner or
exclusive licensee (with the full right to sublicense under any license
agreement, without the necessity of obtaining any consents except Scherer) of
the patent(s) or patent applications in the Territory which claim
fast-dissolving drug delivery systems which Scherer owns or under which Scherer
is licensed with the right to sublicense (the “Patent Rights”); Exhibit A
contains a complete and accurate listing of the Patent Rights (plus certain
other patent rights outside of the Territory, to which Elan makes no
representation or warranty) as of the date of the Scherer Agreement, which Elan
has no reason to believe is inaccurate or incomplete; and to Elan’s knowledge,
the Patent Rights are unencumbered by any lien, charge, claim or encumbrance of
any kind.


 


(c)                             from now through the
expiration or termination of this Agreement or the exercise of the Option,
whichever first occurs, Elan shall not convey, sell, transfer, license, assign
or encumber any interest in any of the Rights, including without limitation the
Information or Patent Rights, or agree to do any of the foregoing.


 


6.2.                                   Amarin.  Amarin represents and warrants that it has the full right and
authority, and has taken all necessary corporate action, to enter into and
perform its obligations under this Agreement and, if the Option is exercised,
enter into the Assignment Agreement as set forth in this Agreement.  Amarin warrants that its entering into and
performing this


 


8

















 


Agreement will
not conflict with or create a default under any agreement or obligation binding
on Amarin.  Following the exercise of
the Option, Amarin shall not sell, assign, transfer, convey, license or
otherwise substantially dispose of the Rights in and to the Product to a third
party (except as provided in Section 10.3 below) without the prior written
consent of Elan, not to be unreasonably withheld.


 


7.                                           Financial Terms; Milestone Payments, Royalty


 


7.1.                                   Milestone Payment.


 


7.1.1                             Amarin shall pay Elan a
one-time milestone payment based upon annual revenues from the sale of the
Product in the Territory of Ten Million Dollars ($10,000,000) payable within
sixty (60) days of the end of the first successive twelve months in which Net
Sales of the Product in the Territory in that twelve month period exceed twenty
million dollars ($20,000,000).


 


7.1.2                             Subject to Sections 7.1.6 and
7.1.7, the said payment shall be made in ordinary shares of £1 each in the
capital of Amarin (“Ordinary Shares”) and shall be calculated
as follows:


 


7.1.2.1                           in the event that the 30 day
trailing average (closing market mid-price) of the Amarin ADR on NASDAQ (the “Price
Average”) on the 30 trading days preceding the date the milestone is
payable is US$6 or less:


 


	
  No. of
  Amarin Ordinary Shares=

  	
  US$10,000,000

  	
   

  
	
   

  	
  the Price
  Average

  



 


7.1.2.2                           in the event that the Price
Average is in excess of US$6 then the number of Ordinary Shares to be issued to
Elan shall be 1,666,667.


 


7.1.3                             Elan shall be entitled to have
such shares, or American Depositary Receipts representing them (“ADRs”)
registered on NASDAQ or any other recognised securities exchange on which
Amarin’s shares or ADRs are traded.  For
that purpose, Elan and Amarin shall enter into a registration rights agreement
in substantially similar form to that certain registration rights agreement
dated as of 21 October 1998 between Amarin (sub nom Ethical Holdings
plc.) and Monksland Holdings B.V., as amended by that certain Amendment No. 1
to Registration Rights Agreement And Waiver between Amarin, Monksland Holdings
B.V. and Elan International Services, Ltd. dated 27 January 2003.  Amarin shall be responsible for all costs,
fees, duties and taxes whatsoever relating to such registration, including
depositary’s fees, NASDAQ fees, stamp duty and stamp duty reserve tax.


 


9

















 


7.1.4                             The right to this payment and
associated rights will be freely assignable by Elan, whether or not in
association with the assignment of other rights in relation to the Product.


 


7.1.5                             As at the date of this
Agreement, each ADR represents one Ordinary Share.  The Assignment Agreement will take into account any change in
Amarin’s share or ADR structure prior to its execution, and will further
contain customary provisions regarding the preservation of value of this payment
in the event of stock splits, consolidations, takeovers, mergers, further share
issues and other events.


 


7.1.6                             Section 7.1.2 shall not
be effective (and Elan shall not receive such payment in Ordinary Shares)
unless and until Amarin receives all necessary shareholder, regulatory and
governmental consents and approvals to so so without material conditions,
including authority to issue and allot the Ordinary Shares, to disapply
pre-emption rights in respect of them, other shareholder approval and/or the
approval of the Panel of Takeovers and Mergers, London.


 


Amarin shall use its best commercial
efforts to secure all such consents and approvals and to maintain them in force
at all material times.


 


Without prejudice to the generality of the
foregoing, Amarin shall seek requisite approvals from its shareholders in the
course of each general meeting convened after the date of this Agreement.


 


If, at the time at which payment is to be
made, Amarin does not have all such consents and approvals, Amarin shall
instead pay to Elan in immediately available funds:


 


(a)                        if the Price Average is
US$6.00 or less, US$10,000,000 (Ten Million Dollars);


 


(b)                       if the Price Average is
greater than US$6.00, the Price Average multiplied by 1,666,667.


 


7.1.7                             In the event that, prior to
the said milestone payment falling due, there is a Change of Control in Amarin
(meaning mean circumstances where any third party shall, directly or
indirectly, acquire fifty percent (50%) or more of the then voting stock of
Amarin, or otherwise merge, consolidate or enter into any similar transaction
(or binding agreement in respect thereof) with Amarin in a transaction after
which Amarin is not the controlling entity):


 


7.1.7.1                           the said milestone payment
shall instead be payable in cash, by wire transfer of immediately available
funds (but without changing its due date);


 


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7.1.7.2                           the amount of such cash
payment shall be the greater of (a) US$10,000,000 (Ten Million Dollars) and (b)
the product of (i) 1,666,667 and (ii) the acquisition price of Amarin’s
ADRs.  For this purpose the “acquisition
price” shall mean the value per ADR received by their holders generally,
including any contingent value actually realised by such holders in due course.


 


7.2.                                   Calculation. “Net Sales” shall mean the
aggregate gross sales of the Product by Amarin and its Affiliates (other than
sales among Amarin and its Affiliates) determined in accordance with UK
generally accepted accounting principles, consistently applied (“GAAP”),
less the following as specifically incurred for the Product: cash, trade or
quantity discounts; sales, use, tariff, or other excise taxes imposed upon
particular sales; transportation charges; and other credits or allowances,
including those granted on account of prices, adjustments, wholesaler
chargebacks, returns or rebates, if any are incurred or granted.  In connection with all amounts based upon
Net Sales payable to Elan pursuant to this Agreement, upon Elan’s request
Amarin shall provide documentation supporting any of the deductions to Net
Sales set forth above.  Any other sales
or transfers among Amarin or Amarin Affiliates shall not be included in the
definition of Net Sales.  In such cases
Net Sales shall be determined based on the invoiced sale price by the Affiliate
to the first third party trade purchaser, less the deductions allowed under
this definition.  Deductions to arrive
at Net Sales shall be determined in accordance with GAAP.  Elan shall have the right, upon reasonable
advance written notice to Amarin and during regular business hours, to inspect
the records of Amarin relating to the calculation of Net Sales hereunder.  Such inspection shall be conducted by an
independent third party auditor chosen by Elan and reasonably acceptable to
Amarin.  Such inspection shall be at Elan’s
cost, unless a discrepency in payment of more than 5% is found, in which case,
it shall be at Amarin’s cost.  The
parties shall reconcile any discrepancy found within 30 days of receipt of the
report of the auditor.  Elan’s audit
right, as described, shall survive any expiration or termination of this
Agreement, such that Elan’s right shall survive one (1) year beyond payment by
Amarin of the final payment to Elan owed hereunder.


 


7.3.                                   Royalty Payments.


 


7.3.1                             Subject to Clause 7.3.2, for
the first eight (8) Launch Years, Amarin shall pay Elan a royalty of twelve and
one-half percent (12.5%) of Net Sales during that period, payable no more than
forty-five (45) days from the end of each calendar quarter for which a payment
is due.


 


7.3.2                             Where Amarin makes one or more
payments to Elan under Clause 9 of the Master Agreement, each whole
US$1,000,000 of such payment (or payments in aggregate) shall reduce the
royalty payable to Elan by one half of one percent (0.5%) as from the calendar
quarter after the payment is made.


 


11

















 


Accordingly, payment of the maximum amount
of US$10,000,000 under Clause 9 of the Master Agreement shall reduce the
royalty by 5%, from 12.5% to 7.5%.


 


7.3.3                             Amarin shall not be entitled
to reduce the royalty payable in this manner other than by payments required
under Clause 9 of the Master Agreement or with the prior written consent of
Elan.


 


7.4.                                   Payment Terms.  Payments shall not be refundable or subject to any future
performance obligations of Elan to Amarin and shall not be applicable against
any future services provided by Elan to Amarin.


 


8.                                           Termination


 


8.1.                                   The Option shall terminate
without further notice or action upon the expiration of the Option Period if
Amarin fails to timely and properly exercise the Option as provided in this
Agreement and during the Option Period.


 


8.2.                                   The Option shall terminate
without further notice or action in the event that Amarin has not paid to Elan
and its Affiliates the sum of US$30,000,000 (thirty million dollars) under
Clause 7 of the Master Agreement or otherwise expressed to be in discharge of
the Outstanding Amounts (as defined in the Master Agreement), on or before 31
December 2003.


 


8.3.                                   Amarin may terminate the
Option prior to expiration of the Option Period at any time only by  notifying
Elan in a writing (signed by the CEO or the President of Amarin) of its
decision not to exercise the Option and specifically referring to this
Agreement.


 


8.4.                                   Elan may terminate this
Agreement and the Option in the event that:


 


(a)                             Amarin breaches any Elan
Agreement and does not remedy it within thirty (30) days of written notice of
such breach from Elan specifying in reasonable detail the nature of the breach
and requesting the same to be remedied, the expiry of such thirty (30) day
period ;


 


(b)                            Amarin is unable to pay its
debts as they fall due, commences negotiations with any one or more of its
creditors (other than Elan and/or Elan Affiliates) with a view to the general
readjustment or rescheduling of its indebtedness or makes a general assignment
for the benefit of or composition with its creditors;


 


(c)                             Amarin takes any corporate
action or other steps are taken or legal proceedings are started for its
winding up (which are not dismissed or struck out within seven days of
presentation), or for its dissolution, administration or re-organisation (other
than in connection with a bona fide solvent restructuring) or for the
appointment of a liquidator, receiver, administrator, administrative receiver,
trustee or similar officer of it or of all or a substantial part of its
revenues and assets; or


 


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(d)                            any execution or distress is
levied against, or an encumbrancer takes possession of, the whole or any
substantial part of, the property, undertakings or assets of Amarin or any
event occurs which under the laws of any jurisdiction has a similar or
analogous effect.


 


9.                                           Default


 


Subject
to Section 6.2 above, if either party fails to perform or fulfill at the
time and in the manner herein provided any material obligation or condition
required to be performed by such party (the “Defaulting Party”) hereunder,
and if such Defaulting Party fails to remedy such default within thirty (30)
days after written notice thereof from the non-defaulting party, the
non-defaulting party shall have the right to immediately terminate the
Agreement and the Option by written notice to the Defaulting Party, in addition
to any other rights it may have.


 


10.                                    Miscellaneous.


 


10.1.                             Notices. Any consent, notice or
report required or permitted to be given or made under the Agreement by  one
of the parties hereto to the other party shall be in writing, delivered
personally or by facsimile (and promptly confirmed by personal delivery, U.S.
first class mail or courier), U.S. first class mail or courier, postage prepaid
(where applicable), addressed to such other party at its address indicated
below, or to such other address as either party may notify the other in
accordance with this Section, and (unless otherwise provided in this Agreement)
shall be effective upon receipt by the addressee.


 


If to Amarin:


 


Amarin Corporation, plc


7 Curzon Street


London W1Y 7FL, UK


Attention: CEO


Facsimile: 
+44-207-499-9004


Attn:  Chief
Executive Officer


 


with a copy to:


 


Amarin Corporation, plc


Two Belvedere Place, Suite 330


Mill Valley, California  94941


Attention: 
Executive Vice President, Legal


Facsimile: 
415-389-4756


 


If to Elan:


 


Elan Pharma International Limited


c/o Elan International Services Ltd


102 St. James Court, Flatts,


Smiths FL04, Bermuda


Attention: 
Director


Facsimile: 
441-292-2224


 


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10.2.                             Governing Law.  The Agreement shall be governed by and construed in accordance
with the laws of the State of Delaware, without regard to the conflicts of law
principles thereof.


 


10.3.                             Assignment.  Subject to Elan’s rights of termination in Section 8.4 and
Section 9, neither party shall assign its rights or obligations under the
Agreement without the prior written consent of the other party hereto; provided,
however, that either party may, without such consent, assign the
Agreement and its rights and obligations hereunder to an affiliate, or in
connection with the transfer or sale of all or substantially all of its assets
or business, or in the event of its merger or consolidation or change in
control or similar transaction (again subject to Elan’s right in the event of
an Amarin Change of Control), and provided further that any permitted
assignee assumes in writing all obligations of its assignor under this
Agreement.


 


10.4.                             Waivers and Amendments.  No change, modification, extension, termination or waiver of this
Agreement shall be valid unless made in writing and signed by duly authorized
representatives of the parties.


 


10.5.                             Entire Agreement.  This Agreement, together with the exhibits hereto, embodies the
entire understanding between the parties and supersedes any prior understanding
and agreements between and among them respecting the subject matter, including
the Original Agreement.  There are no
representations, agreements, arrangements or understandings, oral or written,
between the parties relating to the subject matter of the Agreement which are
not fully expressed herein.


 


10.6.                             Counterparts.  The Agreement may be executed in two or more counterparts, each
of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.


 


10.7.                             Further Assurances.  The parties shall take any other actions, including without
limitation the execution and delivery of documents, as may be reasonable,
necessary or appropriate to carry out the intent of this Agreement.


 


14

















 


[Signature Page: Zelapar
Amendment]


 


	
  SIGNED

  
	
   

  
	
   

  	
   

  
	
  For and on
  behalf of

  
	
  ELAN PHARMA INTERNATIONAL LIMITED

  
	
   

  
	
   

  
	
  SIGNED

  
	
   

  
	
   

  	
   

  
	
  For and on
  behalf of

  
	
  AMARIN CORPORATION PLC.

  



 


15

















 


EXHIBIT A    PATENT RIGHTS


 


The remainder of this page is intentionally blank.  The following unnumbered pages constitute
Exhibit A.


 


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